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What causes human cancer? Approaches from the chemistry of DNA damage

Overview of attention for article published in Genes and Environment, July 2016
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Title
What causes human cancer? Approaches from the chemistry of DNA damage
Published in
Genes and Environment, July 2016
DOI 10.1186/s41021-016-0046-8
Pubmed ID
Authors

Hiroshi Kasai

Abstract

To prevent human cancers, environmental mutagens must be identified. A common mechanism of carcinogenesis is DNA damage, and thus it is quite possible that environmental mutagens can be trapped as adducts by DNA components. It is also important to identify new types of DNA damaging reactions and clarify their mechanisms. In this paper, I will provide typical examples of our efforts to identify DNA damage by environmental agents, from chemistry-based studies. 1) Oxidative DNA damage: 8-Hydroxydeoxyguanosine (8-OHdG, 8-oxodG) was discovered during a structural study of DNA modifications caused in vitro by heating glucose, which was used as a model of cooked foods. We found that various oxygen radical-forming agents induced the formation of 8-OHdG in DNA, in vitro and in vivo. Analyses of the urinary 8-OHdG levels are useful to assess the extent of oxidative DNA damage in a human population. 2) Lipid peroxide-derived DNA adducts: We searched for mutagens that react with deoxynucleosides, in model systems of lipid peroxidation. The reaction mixtures were analyzed by high performance liquid chromatography (HPLC), and we discovered various lipid peroxide-derived mutagens, including new mutagens. Some of these adducts were detected in human DNA. These mutagens may be involved in lipid peroxide-related cancers. 3) Methylation of cytosine by free radicals: Methylation of the cytosine C-5 position is an important mechanism of carcinogenesis, in addition to gene mutations. However, the actual mechanisms of de novo methylation in relation to environmental agents are not clear. We found that cytosine C-5 methylation occurred by a free radical mechanism. The possible role of this radical-induced DNA methylation in carcinogenesis will be discussed, in relation to the presently accepted concept of cancer epigenetics. In these studies, chemical analyses of the adducts formed in model reactions led to the discoveries of new mutagens and important types of DNA modifications, which seem to be involved in human carcinogenesis.

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The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 64 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Belgium 1 2%
Unknown 62 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 11%
Student > Bachelor 7 11%
Student > Master 6 9%
Researcher 5 8%
Other 3 5%
Other 6 9%
Unknown 30 47%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 8 13%
Medicine and Dentistry 7 11%
Agricultural and Biological Sciences 5 8%
Chemistry 3 5%
Pharmacology, Toxicology and Pharmaceutical Science 2 3%
Other 7 11%
Unknown 32 50%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 October 2016.
All research outputs
#14,388,865
of 25,374,917 outputs
Outputs from Genes and Environment
#52
of 135 outputs
Outputs of similar age
#188,215
of 367,263 outputs
Outputs of similar age from Genes and Environment
#5
of 6 outputs
Altmetric has tracked 25,374,917 research outputs across all sources so far. This one is in the 42nd percentile – i.e., 42% of other outputs scored the same or lower than it.
So far Altmetric has tracked 135 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.9. This one has gotten more attention than average, scoring higher than 61% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 367,263 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 48th percentile – i.e., 48% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one.